by Medical implants can be life-saving or significantly improve quality of life, but to our immune system they can appear as invaders.
Rice University biochemist Omid Veiseh and his colleagues discovered that the deposition of lipids on the surfaces of implants can play a mediating role between the body and the implants, with some lipids acting as peacemakers while others cause conflict.
“We learned that as immune cells crawl into an implanted biomaterial, they leave behind lipid vesicles that signal to the host’s immune system whether the biomaterial should be ignored or removed from the body,” said Veiseh, assistant professor of bioengineering and cancer prevention at Rice. and Texas Research Institute Fellow.
This knowledge could help scientists develop biomaterials or coatings for implants that deflect host immune system aggression, reducing malfunction rates for biomedical devices such as pacemakers, cerebrospinal fluid drains, coronary stents, surgical mesh, drug delivery pumps, biosensors and more.
The study is published in Advanced Materials.
“A major problem with all biomedical implants is that the immune system attacks them,” said Christian Schreib, a Rice graduate student and lead author of the study. “Essentially, it encases them in a fibrous capsule that destroys their functionality and makes them no longer work.”
“Our team was able to develop a chemical surface modification that preferentially recruits macrophages that leave behind a ‘don’t attack’ lipid vesicle signature that allows the implants to exist in the body without being recognized as foreign,” said Veiseh.
Fibrosis, or scarring, is the accumulation of excess tissue at the site of injury. The fibrotic response to implants has traditionally been associated with the deposition of proteins on the implanted surface.
“In our research, we realized that while proteins are important, fat molecules also play an important role in the fibrotic process,” Schreib said. “We identified two lipid profiles, fatty acids and phospholipids. Fatty acids are more likely to trigger an immune response, while phospholipids are more likely to fly under the radar and not bother the immune system.
“Now that we understand that, we can use this knowledge to make materials for use in implants that are less likely to cause an immune response. We could, say, make a material that attracts phospholipids to it, so that when you implant the The material, phospholipids are naturally deposited on it and help it evade the immune system. We might also want to look at taking these fat molecules like phospholipids and chemically functionalize them on the surface of the device before implantation.”
When an immune response is triggered in the body, cells of the immune system are mobilized to the site of injury or invasion. Increased circulation of immune system cells near the implant leads to greater accumulation of fibrous tissue.
“A thick layer of cells deposited on the implant is likely to prevent it from working,” Schreib said. “But if you have a lipid layer at the atomic scale, that’s not going to affect its functionality to the same degree.”
Optimizing the performance of implants is most critical for groups of patients who rely on them to manage chronic and potentially life-threatening conditions such as hydrocephalus, a disorder involving excessive accumulation of cerebrospinal fluid (CSF) in the brain. For many patients, the only effective management strategy is the placement of a CSF drain that diverts excess fluid to a different body cavity. Pediatric patients with hydrocephalus experience particularly high rates of implant failure, which can lead to headaches, vomiting, vision loss, brain damage, and death if not treated quickly.
“As a pediatric neurosurgeon, it’s safe to say that branching dysfunction is the bane of my existence,” said Dr. Brian Hanak, assistant professor of neurosurgery at Loma Linda Children’s University in California, who is a co-author of the study. While CSF shunt dysfunction can occur in any age group, rates of dysfunction are much higher in young children. “Most of us who work in this area believe that this is probably related to the fact that the brain’s innate immune system is being renewed especially in young children,” he said.
“In young children and babies, shunt malfunction rates are in the 40%-50% range two years after implantation. Frankly, I am embarrassed to routinely implant the most failure-prone life-sustaining device in modern medicine. You developed a pacemaker with a 40% to 50% failure rate at two years, it would never get FDA approval because that’s horrible. But unfortunately that’s the industry standard for CSF bypasses.”
Hanak said that many brain implants could benefit from a reduced innate immune response.
“One in particular that always comes to mind is brain-computer interface technology,” he said. “It’s been about 20 years now since we had a proof of concept that you can implant a microelectrode array in someone’s brain and have them use that array to control a robotic arm.
“You might ask, if that’s the case, then why isn’t this technology something that every paralyzed person can use to improve their independence and quality of life? The reason is that the immune response that’s placed on these implanted electrode arrays it makes him unable to record neuronal activity beyond two to three years in vivo. Right now, with the current state of our technology, it’s not really a viable solution, certainly not a long-term solution for paralyzed patients.”
The National Institutes of Health (R01 DK120459), the Defense Advanced Research Projects Agency (D20AC00002), a Rice University Academy Fellowship, the Shared Equipment Authority at Rice, and the National Science Foundation (CBET1626418) supported the research.
